RESUMO
OBJECTIVE: To test the hypothesis that smooth muscle cells of the human umbilical vein have vasoconstricting endothelin B (ETB) receptors. METHODS: In strip preparations of human umbilical veins isometric tension after exposure to the selective ETB receptor agonist sarafotoxin S6c (S6c) was compared to the tension before S6c exposure (set as 100%). RESULTS: In intact preparations S6c induced vasoconstriction only at the highest concentration applied (10(-8)M; 149.5 +/- 12.5 vs. 100%, p < 0.05). In contrast, in endothelium-denuded preparations S6c induced vasoconstriction already at the lowest S6c concentration investigated (10(-11)M; 111.7 +/- 4.3 vs. 100%, p < 0.05). CONCLUSIONS: The vasoconstricting effect of S6c in endothelium-denuded human umbilical vein preparations points to smooth muscle cell ETB receptor activation.
Assuntos
Músculo Liso Vascular/fisiologia , Receptor de Endotelina B/fisiologia , Veias Umbilicais/fisiologia , Vasoconstrição , Vasoconstritores/farmacologia , Venenos de Víboras/farmacologia , Humanos , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Veias Umbilicais/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosRESUMO
Non-oliguric hyperkalaemia is a common and serious complication of extreme prematurity, resulting from a potassium loss from the intra- into the extracellular space during a specific post-natal period. Treatment of this disorder has been adapted from the treatment of hyperkalaemia in renal failure, an entity of completely different pathophysiology. A few years ago, the administration of salbutamol, which induces cellular potassium uptake, was proposed as a new therapeutic option. In this review article we discuss the pathogenesis and current therapy of non-oliguric hyperkalaemia of the premature infant, with special emphasis on the presently available knowledge and concerns with regard to the use of salbutamol. Being aware of the paucity of studies on non-oliguric hyperkalaemia, we propose treatment recommendations which are based on best available evidence. These comprise the administration of calcium, infusion of insulin plus glucose, correction of acidosis, and exchange transfusion or peritoneal dialysis as a last resort therapy. Before controlled trials on efficacy of salbutamol treatment of non-oliguric hyperkalaemia of the premature infant can be initiated, more data on safety are needed.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Hiperpotassemia/etiologia , Hiperpotassemia/terapia , Doenças do Prematuro/etiologia , Doenças do Prematuro/terapia , Agonistas Adrenérgicos beta/farmacologia , Albuterol/farmacologia , Cálcio/uso terapêutico , Diuréticos/uso terapêutico , Medicina Baseada em Evidências , Transfusão Total , Glucose/uso terapêutico , Humanos , Hiperpotassemia/metabolismo , Hipoglicemiantes/uso terapêutico , Recém-Nascido , Doenças do Prematuro/metabolismo , Insulina/uso terapêutico , Neonatologia/métodos , Neonatologia/normas , Diálise Peritoneal , Guias de Prática Clínica como Assunto , Fatores de Risco , Segurança , Bicarbonato de Sódio/uso terapêutico , Resultado do TratamentoRESUMO
In a previous study, human umbilical vein preparations constricted at PO(2) values above the physiologic intrauterine PO(2) range and dilated at hypoxia. Denudation of the endothelium reversed the hypoxic vasodilatation only, suggesting the release of a nonendothelial vasoconstrictor. We therefore hypothesized that norepinephrine from adrenergic nerve terminals could be responsible for the observed constricting effects. We measured intracellular membrane potential and isometric tension of human umbilical vein strips with and without functional adrenergic denervation by 6-OH-dopamine during variation of PO(2). With PO(2) increasing from 5 to 104 mm Hg, intact preparations depolarized of from -58.6 +/- 1.1 mV (SEM) to -53.3 +/- 1.0 mV (p < 0.001) and isometric tension increased from 0.673 +/- 0.037 g to 0.825 +/- 0.044 g (p < 0.02). Intact preparations pretreated with 6-OH-dopamine depolarized from -58.0 +/- 0.5 mV to -55.8 +/- 0.6 mV (p < 0.01), and isometric tension increased from 0.598 +/- 0.040 g to 0.661 +/- 0.018 g (p < 0.02). At Po(2) values above the physiologic intrauterine umbilical venous Po(2) range, membrane potential and isometric tension were significantly lower in preparations with 6-OH-dopamine pretreatment compared with matched controls (p < 0.05). Denudation of the endothelium reversed the hypoxic hyperpolarization and vasodilatation observed in intact preparations. However, membrane potential and isometric tension were not different between endothelium-denuded preparations with and without 6-OH-dopamine pretreatment. We conclude that locally released norepinephrine contributes to the depolarization and vasoconstriction of the human umbilical vein at hyperoxia but does not antagonize the endothelium-dependent vasodilation at hypoxia.
Assuntos
Norepinefrina/metabolismo , Oxigênio/farmacologia , Veias Umbilicais/metabolismo , Vasoconstrição/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Humanos , Técnicas In Vitro , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Oxidopamina/farmacologia , Simpatolíticos/farmacologia , Vasoconstrição/efeitos dos fármacosRESUMO
We investigated the possible contribution of nitric oxide (NO) and endothelin (ET) to oxygen-dependent regulation of human umbilical vein vascular tone by simultaneous registration of intracellular membrane potential and isometric tension of vessel strips with and without NO synthase inhibition [10-4 M N omega-nitro-L-arginine methyl ester (L-NAME)], ETA receptor blockade (10(-5) M BQ-123), or ETB receptor blockade (10(-7) M BQ-788) at Po2 values in the bath solution between 5 and 104 mmHg. Increasing PO2 above the physiological intrauterine range resulted in depolarization and an increase of isometric tension, whereas lowering PO2 resulted in hyperpolarization and a decrease in isometric tension. Removal of the endothelium reversed these effects. At PO2 values below 39 mmHg, intact preparations treated with either L-NAME, BQ-788, or BQ-123 were more depolarized than controls. In the case of treatment with L-NAME or BQ-123, this was accompanied by an increase in isometric tension. We conclude that it is NO that mediates the hypoxic hyperpolarization and vasodilatation of the human umbilical vein and that ET, via activation of ETB1 receptors on endothelial cells, contributes to this effect.
Assuntos
Endotelinas/fisiologia , Óxido Nítrico/fisiologia , Oxigênio/fisiologia , Veias Umbilicais/fisiologia , Sistema Vasomotor/fisiologia , Antagonistas dos Receptores de Endotelina , Inibidores Enzimáticos/farmacologia , Humanos , Técnicas In Vitro , Contração Isométrica , Potenciais da Membrana/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Oligopeptídeos/farmacologia , Oxigênio/metabolismo , Pressão Parcial , Peptídeos Cíclicos/farmacologia , Piperidinas/farmacologia , Receptor de Endotelina A , Receptor de Endotelina B , Vasoconstrição , Sistema Vasomotor/efeitos dos fármacosRESUMO
AIM: To investigate the contribution of prostanoids to the oxygen-dependent regulation of human umbilical vein vascular tone. METHODS: Intracellular membrane potential and isometric tension of intact and endothelium-denuded human umbilical vein strips with and without cyclooxygenase inhibition by indomethacin (10(-5) M) were recorded simultaneously during variation of the local pO2. RESULTS: Decreasing pO2 from 39 to 5 mm Hg resulted in hyperpolarization and decrease in isometric tension of intact preparations. These effects did not occur in indomethacin treated preparations. Endothelium-denuded preparations revealed pronounced depolarization and increase in tension with decreasing pO2. Indomethacin treatment abolished these effects. With increasing pO2 from 39 to 104 mm Hg intact preparations depolarized and isometric tension remained stable. Removal of the endothelium or treatment with indomethacin reversed these effects. CONCLUSIONS: This study confirms that the human umbilical vein actively regulates its vascular tone which is under the control of PO2. Vasodilating endothelial prostanoids contribute to the hypoxic vasodilatation and thereby counteract the vasoconstricting actions of prostanoids released from vascular smooth muscle cells. Our results indicate that vasoconstricting prostanoids are released from the endothelium of the human umbilical vein at hyperoxia.
Assuntos
Contração Muscular/efeitos dos fármacos , Prostaglandinas/farmacologia , Veias Umbilicais/efeitos dos fármacos , Vasodilatadores/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Humanos , Indometacina/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Oxigênio/farmacologia , Gravidez , Prostaglandinas/administração & dosagem , Valores de Referência , Veias Umbilicais/fisiologia , Vasodilatadores/administração & dosagemRESUMO
UNLABELLED: Preterm newborn infants are especially susceptible to Gram-negative sepsis that is associated with a lethality of up to 40%. AIMS: We tested whether polymorphonuclear leukocytes (PMN) from preterm infants exhibit an impaired antibacterial response upon stimulation with lipopolysaccharide (LPS) from Escherichia coli when compared to full term newborns or adults. METHODS: We studied the effect of LPS on the expression of the surface proteins CD11b and CD14 and the secretion of elastase by PMN from preterm infants, term infants and adults ex vivo. RESULTS: We found a significantly reduced antibacterial activity of PMN from preterm infants upon stimulation with LPS as indicated by low surface expression of the adhesion molecule CD11b and the reduced secretion of PMN elastase. LPS-induced CD11b expression was dependent on binding of LPS to the surface protein CD14 as CD14 antibodies inhibited LPS dependent CD11b upregulation. Furthermore CD14 expression was lower on PMN from preterm infants than from adults. In addition, CD14 independent upregulation of CD11b in response to tumor necrosis factor (TNF-alpha), N-formyl peptides (FMLP) and phorbol ester (PMA) was impaired. CONCLUSION: PMN from preterm infants are distinctly hyporesponsive to LPS, which may explain the predisposition of these children to invasive disease due to gramnegative bacteria.
Assuntos
Recém-Nascido Prematuro/imunologia , Receptores de Lipopolissacarídeos/imunologia , Neutrófilos/imunologia , Adulto , Antígeno CD11b/imunologia , Antígenos CD18/imunologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/imunologia , Feminino , Humanos , Recém-Nascido , Elastase de Leucócito/imunologia , Lipopolissacarídeos/imunologia , Gravidez , Sepse/imunologia , Sepse/microbiologiaRESUMO
Nonoliguric hyperkalemia of premature infants probably results from a transient inhibition of membrane-bound Na+/K+-ATPase during the first 24 h after birth. We hypothesized that the endogenous digitalis-like activity of the serum of premature infants, which inhibits the Na+/K+-ATPase, triggered hyperkalemia. Serum concentrations of potassium ([K+]) and of the digoxin-like immunoreactive substance ([DLIS]) were measured during the first 24 h after birth in 60 infants including 30 infants <30 gestational weeks. Contrary to our hypothesis, there was a negative linear correlation between [DLIS] at birth and [K+] 24 h after birth (r2 = 0.24, p < 0.002). 24 h after birth there was no correlation between [DLIS] and [K+]. Thus, a major role of DLIS in nonoliguric hyperkalemia could not be established.
Assuntos
Digoxina/metabolismo , Espaço Extracelular/metabolismo , Hiperpotassemia/etiologia , Hiperpotassemia/metabolismo , Potássio/metabolismo , Saponinas/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Cardenolídeos , Ritmo Circadiano , Digoxina/sangue , Feminino , Humanos , Hiperpotassemia/sangue , Recém-Nascido , Líquido Intracelular/metabolismo , Masculino , Concentração Osmolar , Potássio/sangue , Saponinas/sangue , Fatores de TempoRESUMO
Complment activation during extracorporeal membrane oxygenation (ECMO) in newborns can be caused by both the underlying disease processes and by blood contact with the ECMO circuit. We investigated the relative importance of these mechanisms by measuring C3a, C5a and sC5b-9 before, during and after neonatal ECMO in six consecutive newborn patients using enzyme-linked immunoassay. In addition complement activation during in vitro ECMO with repeated flow of the same blood volume was measured using blood from healthy adult donors. C3a increased significantly in vivo after 1 h (from 1035+/-193 to 1865+/-419 microg/l) and in vitro ECMO (from 314+/-75 to 1962+/-1062 microg/l). C5a increased during ECMO without significant differences between in vivo and in vitro activation. In neonatal patients, sC5b-9 rose faster than in vitro, but the rapid increase was also significant for in vitro experiments (in vivo: from 328+/-63 to 1623+/-387 microg/l after 2 h; and in vitro: from 78+/-32 to 453+/-179 microg/l after 8 h). After this initial peak at 1-2 h, complement activation decreased gradually until 2-3 days after the initiation of ECMO. We conclude that in newborns the rapid activation of the complement system after the start of ECMO is predominantly caused by contact with artificial surfaces rather than the patient's underlying disease.